Brain-derived neurotrophic factor (BDNF) is one of the most studied members of the neurotrophin family. It is ubiquitously expressed in the central nervous system (CNS) and plays key roles in survival, differentiation, and axonal and dendritic development and maintenance of neurons in both the developing and mature brain[1]. Consequently, studies on rodent and human subjects have shown that BDNF dysregulation in the brain underlies many disease processes, including neuropsychiatric and degenerative diseases, impaired learning, and memory which highlight the important role of BDNF in the health of the CNS[2], [3], [4], [5]. Interestingly, early studies on rodents revealed that BDNF, but not other neurotrophins, also plays a crucial role in the CNS regulation of body weight which was later observed in humans, as well[6], [7], [8]. Heterozygous BDNF knockout mice become significantly heavier than their wild-type counterparts by 12 weeks of age[7] and humans with BDNF haploinsufficiency become severely obese by early childhood[8]. Another remarkable observation was the expression of BDNF and TrkB, its receptor, in human neuroblastoma cell lines and primary human tumors which was associated with poor prognosis factors and advanced stage[9]. In the following years, similar observations have also been made in other solid tumors, including Wilm’s Tumor[10], ovarian[11], endometrial[12], breast[13], lung[14], pancreatic[15], gastric[16], and colon cancers[17]. Mechanistically, BDNF/TrkB signaling pathways in cancer cells have been associated with increased epithelial-to-mesenchymal transition, cell migration, survival, and most noticeably anoikis resistance[11], [12], [18]. These observations strongly suggest an important role for BDNF/TrkB signaling in cancer progression and metastasis. Cancer cachexia is a multisystem disease that is characterized by progressive muscle atrophy with or without fat atrophy which is not responsive to nutritional support[19]. It is a prevalent condition in cancer patients and causes significant morbidity and mortality. Unfortunately, there is no effective treatment for cancer cachexia. In this review, our current knowledge of the role of BDNF in body weight regulation will be overviewed and its possible involvement in cancer cachexia will be discussed.